Granulomatosis with polyangiitis (GPA)In GPA and MPA, there is inflammation of the blood vessels in the body. Both diseases belong to the so-called ANCA-associated small vessel vasculitides and are rather rare: Between five and 12 people (per million population) develop GPA each year. The disease usually occurs between the age of 40. and 50. The disease appears at the age of 18, and both men and women are affected.* MPA affects fewer people – two to three per million population annually. The majority of patients are over 50 years old at the onset of the disease. Men are more frequently affected by MPA than women.*
*Source: Gibelin A et al.; Semin Respir Crit Care Med 2011; 32: 264-273
For better comprehension we have explained some technical terms. You will get the explanations if you move the mouse over the underlined terms.
The facts about GPA
Depending on which vessels are affected, the symptoms of GPA and MPA can occur in the ear, nose, throat, eyes, limbs, or skin. When the organ vessels are involved, symptoms such as high blood prere, paralysis or shortness of breath also occur.
Vasculitis is an inflammatory disease of the blood vessels. Vasculitides can affect the entire organism. Occur as an independent clinical picture without a known trigger. GPA and microscopic polyangiitis (MPA) belong to the so-called primary vasculitides. However, vasculitis can also be the result of another disease (e.g., vasculitis). B. rheumatoid arthritis) or occur as an undesirable side effect of medication – then it would be a secondary vasculitis.
Primary vasculitis such as GPA and MPA is medically classified as an inflammatory rheumatic disease. In all cases, it requires care by a specialist, usually the rheumatologist.
Since there are blood vessels everywhere in the body, vasculitis can in principle affect all vessels and thus also organs, which explains the different symptoms. That is why the complaints sometimes turn out so differently. One speaks therefore also of a systemic illness, thus an illness, with which the whole body is affected. The well-being can be considerably reduced.
GPA is also called "Wegener's granulomatosis" and takes its name from its first describer, the German physician Friedrich Wegener. Recently, experts have agreed to use the term "granulomatosis with polyangiitis". This is for international standardization of terms.
The term "granulomatosis" describes the characteristic changes that are often found in the airways of GPA patients as soon as the tie is examined under the microscope. So-called granulomas, small nodular accumulations of cells are often the discovery of such investigations.
Polyangiitis means that many vessels are inflamed (Greek poly = many; Latin angiitis = vascular inflammation). Microscopic polyangiitis (MPA) is so called because the vessels mainly affected are very small and only visible under the microscope.
In essence, both diseases manifest with very similar symptoms. Unlike GPA, MPA does not involve granulomas and very rarely affects the upper respiratory tract and head. Vasculitides can occur locally in the body, for example in the nose – this is known as the localized form. If, on the other hand, a large number of the body's blood vessels are affected, this is referred to as a generalized form.
Common signs of vasculitis
Fatigue and weakness, fever, night sweats and weight loss as an expression of the inflammation, or an unexplained inflammatory reaction in the blood (see "How is the diagnosis made?")?").
In the ear, nose, and throat (ENT) area
– Chronic inflammation of the nasal mucosa with blocked nose, bloody discharge ("bloody cold") and bloody-crusty bark formation – Chronic middle ear inflammation – Hearing loss, hearing loss
At the eye
– Inflammations in almost all parts of the eye; typical is the "red eye" caused by inflammation of the sclera – visual disturbances – pain in or behind the eye or even protrusion of the eyeball – watering eye due to inflammation of the lacrimal duct
On the musculoskeletal system
– Pain and, less frequently, swelling of the joints – Muscle pain, reduced mobility – Morning stiffness, i.e. reduced mobility of the joints in the morning after getting out of bed
On the skin
– Spot-shaped, purple rash (purpura), especially on the legs – Open ulcers on the skin and mucous membranes that heal poorly or not at all
Involvement of organs and the nervous system
– Numbness and sensory disturbances up to paralysis, especially in the feet if the peripheral nervous system is involved – Stroke or seizure as well as paralysis if the central nervous system (CNS) is involved – Bloody cough and shortness of breath if the lungs are involved – Foaming and reddish urine as well as fluid retention in the legs (edema) – High blood prere if the kidneys are involved – Bloody diarrhea, Bloody diarrhea, often associated with cramping abdominal pain, when the digestive system is involved (rare) – Chest pain and shortness of breath when the heart is involved (rare)
Typical symptoms of GPA in the localized form are chronic sinusitis and bloody rhinitis. In the generalized form, the symptoms include a bloody cough, shortness of breath, joint pain and a skin rash. If the inflammation spreads to the vessels of the kidneys, this is manifested by changes in the urine and even failure of the kidney function.
Patients with MPA often complain of hemoptysis, pinpoint purple rash, and joint pain. The kidneys are also frequently affected by MPA.
In an autoimmune disease, such as vasculitis, the body produces too many antibodies, which often cause inflammation and thus attack its own immune system. In the case of GPA and MPA, these are often the antibodies called ANCA.
What exactly triggers the permanent inflammation in the vessels in primary vasculitides such as GPA and MPA is not fully understood. However, it is clear that an overreaction of the body's immune system plays a significant role.
The healthy immune system
The body's own defense system (immune system), protects us from pathogens that enter our body from the outside. Without an immune system, viruses or bacteria could multiply uncontrollably and lead to disease. The immune system is therefore a kind of "body police" that works with many different "special units" and "special weapons". The most important "special units" of the "body police" are the white blood cells (leukocytes). A special form of white blood cells are the so-called T- and B-cells. B cells mature into plasma cells, which form the most important "special weapons" in the fight against foreign invaders: tailor-made proteins or antibodies. Antibodies recognize pathogens, bind to them and thus render them harmless. The fight against external enemies always follows the same pattern in the form of inflammation: the affected area is red, overheated, swollen and painful.
Inflammation is therefore nothing other than the normal and sensible reaction of our body to a stimulus, for example to pathogens. With the inflammatory reaction, the irritant is fought and eliminated. Once this has happened, the inflammation heals completely and the patient no longer has any complaints. The white blood cells, which are particularly involved in the defense and thus inflammatory reaction, are also called inflammatory cells. These include above all T and B cells.
Diseases caused by an excessive reaction of the immune system against the body's own tie are generally referred to as autoimmune diseases. Vasculitides also belong to this group.
When the defense system overreacts, it becomes too strong. It no longer fights pathogens that threaten us from the outside, but also our own body – more precisely: the blood vessels. The "body police" thus form antibodies that are directed against the body's own tie and thus trigger an inflammation. These antibodies are called auto-antibodies (Greek autos = self) and – like the proper antibodies in a healthy immune system – are also produced by the plasma cells, the mature B cells. In vasculitis, the autoantibodies contribute, among other things, to the chronic inflammation.
Why this autoimmune reaction occurs and why the immune system suddenly overreacts and attacks the body's own components is still not completely clear, despite intensive research work.
In detail: What is ANCA-associated vasculitis??
It is thought that a specific form of auto-antibody, ANCA, may be involved in the development of GPA and MPA. The term ANCA-associated vasculitis (abbreviated AAV) or ANCA-positive vasculitis is therefore used. ANCA are directed against the interior (cytoplasm) of neutrophil granulocytes – a specific group of white blood cells. ANCA are formed by plasma cells, which in turn mature from B cells. B cells thus play a very important role in ANCA-positive vasculitides.
How do the ANCA cause an inflammation of the blood vessel??
It is amed that the ANCA bind to the neutrophil granulocytes, which then release inflammatory messenger substances and activate other inflammatory cells such as T cells. Direct binding of ANCA to the vessel wall is also conceivable. As a result, the entire vessel wall swells, which can lead to constriction or even occlusion of the vessel.
Consequences: The tie supplied by this vessel is no longer sufficiently supplied with blood, oxygen and nutrients and dies; the medical profession refers to this as an "infarct". Inflamed vessels, however, can not only narrow or close, they can also form bulges (aneurysm) and burst (rupture). Then there is a risk of hemorrhage.
This explains why the symptoms of patients are so varied, and the immediate consequences can range from less debilitating to life-threatening. The effects of vasculitis depend on how many vessels are affected, in which organ the inflammation is taking place and how large the inflamed vessel is. In the case of smaller vessels, occlusions and/or bleeding in organs (z.B. In medium-sized and large vessels, vascular occlusions and infarctions occur, often initially without organ damage.
The lack of nutrient and oxygen supply to the body due to vascular inflammation also manifests itself with very general symptoms of disease. Patients are often tired, fatigued, lack appetite and often also report unexplained fever, night sweats and weight loss.
For the diagnosis, a series of tests and samples must be made, often with the collaboration of several specialists. This includes testing blood, urine and kidney values, imaging procedures such as CT or MRI, and taking and examining tie samples.
Due to the rarity of the disease and the "colorful picture" that vasculitis presents with its various symptoms, it often takes a long time for the disease to be recognized. Because every single symptom that occurs with vasculitis can also have a variety of other causes.
Vasculitides like GPA and MPA can therefore usually not be detected with one examination. Information about the symptoms, different clinical findings and the results of the examinations must be combined to. This is often difficult in practice and requires close cooperation of the family doctor/internist with other specialists. Everyone has to look very carefully in their own field for indications of vasculitis, of which you as the affected person sometimes do not even notice yourself.
Diagnosis – often a difficult search
Studies have shown that years often pass between the first symptom and the correct diagnosis of vasculitis. The first steps on the way to diagnosis are therefore a detailed consultation with the doctor, in which possible earlier complaints are recalled, and thorough physical examinations.
– Inflammation values: The inflammation that takes place in the body during vasculitis due to the overreacting immune system can usually be detected in the blood. Typically, the inflammation values are elevated. These include the blood cell sedimentation rate, abbreviated as ESR, and the C-reactive protein, abbreviated as CRP. However, both values increase with every inflammation in the body – not only with vasculitis. Therefore, an elevated ESR and CRP alone do not allow the diagnosis of "vasculitis" to be made. However, they can be a first indication of inflammation in the body. Both values are also well suited for monitoring the course of therapy, as they normalize with successful treatment. -Detection – kidney values: These are once again differentiated into creatinine and urea. Both values must be measured initially and then regularly during the course to monitor kidney function. The disadvantage of these values is that they can rise late, when much kidney tie has already been destroyed. Therefore it is very important to examine your urine regularly.
Whether vasculitis-related inflammation is present in the kidney is most easily determined by examining the urine. In the search for possible kidney involvement, the urine is usually examined by means of a test strip, primarily for protein, white blood cells and red blood cells (erythrocytes), i.e. blood components. Both are not found at all or only in very small amounts in the urine of healthy people. Cylinder-like deformed erythrocytes are also typical. If these changes are detectable in the urine, this is an indication of damage to the kidneys. The urine must then be examined in more detail – preferably by a specialist. Other indications of kidney involvement may be an increase in blood prere or the accumulation of water in the legs. You should therefore measure your own blood prere regularly.
Depending on the symptoms, imaging examinations such as X-rays, ultrasound (medical sonography), magnetic resonance imaging (MRI) and computed tomography (CT) may also be important on the way to diagnosis. For example, the typical granulomas in the lungs or in the ear, nose and throat area can be detected during GPA. Your doctor will decide which examination should be performed on you depending on your symptoms.
Fine tie examination with a microscope
If there is a reasonable suspicion of GPA or MPA, a tie sample is ideally taken from the affected organ – for example, the kidney, nose or lungs. This is called biopsy. The tie sample is then examined under the microscope. This procedure is called fine tie examination or histology. In GPA, there is inflammation of the vessels with the characteristic granulomas that gave the disease its name. In MPA, inflammation of the vessels is also seen, but without the granulomas. A positive finding in the histology is often a sure proof of vasculitis. But even here it can happen that the examination remains negative. Histology is the safest. Best evidence of vasculitis.
The treatment varies greatly with each patient. Depending on the stage of the disease, the response to medication and side effects, and the general physical condition, it can vary. In the treatment of autoimmune diseases, one first tries to bring about a halt in the course of the disease and then to maintain this halt.
Vasculitides such as GPA and MPA used to be feared diseases because there was no effective treatment available. With today's knowledge and medical possibilities, neither of these diseases can be completely cured, but they can usually be treated well and thus controlled.
Remission can be achieved in most patients within one year. Very often, patients are able to return to a normal life, for example, to resume their professional activities. Beside the reaching of a Remission for physicians also the improvement of the quality of life an important therapy goal. Since vasculitides can progress very differently in each patient, there is no uniform therapy according to a single scheme.
The treatment is adapted to the extension, the activity and the course of the disease. The therapy of vasculitides is thus a therapy tailored to the individual patient. The treatment itself and regular monitoring of the course of the disease should be carried out by a specialized doctor. Specialists from different disciplines work together to diagnose and treat vasculitis. As mentioned earlier, vasculitides are among the rheumatic diseases. Since the rheumatologist is specialized in autoimmune diseases, the rheumatologist should be in charge of the treatment and its control.
Basically, the therapy of GPA and MPA can be divided into two sections:
– With the so-called remission induction therapy, one wants to initiate remission quickly at first. – In very early stages (localized to the head) of GPA, the antibiotic cotrimoxazole may be prescribed in some cases, which often leads to improvement. – Mild disease courses, especially without kidney or other life-threatening organ involvement, are usually treated with methotrexate (MTX) or even azathioprine (AZA) in combination with cortisone. – Patients with severe courses receive cortisone and cyclophosphamide. Cortisone is always necessary in the beginning, as it acts very quickly. – Recently, the B-cell therapy Rituximab has become available for the remission induction therapy of severe courses, which is also given in combination with cortisone. – Once remission has occurred, induction therapy can be stopped and subsequent treatment to maintain remission can be started. As the name suggests, the aim is to keep the disease at a standstill for as long as possible and to prevent a relapse. – In patients with impaired kidney function, azathioprine is usually prescribed, and less frequently, for example, in the case of intolerance to azathioprine, mycophenolic acid or leflunomide. – If kidney function is normal, MTX may also be given. The question of how long the treatment of a GPA or MPA lasts in total varies from patient to patient and cannot be answered in a generalized way.
Please note: Even if vasculitis is completely repressed after successful treatment, regular visits to the doctor and checks of your condition and blood are necessary. This is how a recurrence of the disease (relapse) can be detected in time. Again, start treatment early or adjust treatment as needed.
The best advocate for your condition is yourself, so the doctors treating you are crucially dependent on your assistance. If you know well about your disease, your course may be more comfortable. Watch for possible "early warning" signs of a new flare-up of the disease – for example, new joint pain, skin changes, ear, nose and throat discomfort, general feeling of illness, unexplained fever or weight loss and gain, and night sweats. Go to the doctor in time. Then the appropriate medication can be started immediately, and the relapse and its consequences may be less severe.
Many medications have undesirable side effects in addition to their effects (e.g., infections). B. Infections), which are often indistinguishable from an attack of the underlying disease. If in doubt, you or your attending physician should consult a rheumatologist. Also, inquire early about possible side effects of the medications you have been prescribed.
Patient training, which is now offered by many rheumatology clinics, is certainly also very useful and important in the proper management of your disease. Here you will get to know other patients and learn about the different medications, early warning symptoms and what else you can do to get your disease under control. For many of those affected, the exchange in self-help groups is also helpful. And another tip: As a patient with GPA. MPA an entitlement to a severe disability card. Officially this is called "application according to the law for severely handicapped persons". This brings various advantages, above all special protection against dismissal and tax benefits. Talk to your supervising physician about this; he or she can give you comprehensive advice on this.
What else you can do:
– Under the therapy with the medicines you should be vaccinated regularly. Your doctor will be happy to advise you on this. – If you have been prescribed cortisone, you should take vitamin D3 to protect your bones. Your doctor will also be pleased to advise you on this subject. Pay attention to a healthy. Balanced diet. A special "rheumatism diet" does not exist. – Do regular sports – when your state of health allows it again. – If you have smoked so far, you should stop this for your own health.
Possible side effects of drug treatment:
With every effective treatment applies: no effect without side effect. Immunosuppressants throttle the exuberant immune system, but unfortunately also the function of the healthy immune system. Therefore, infections generally occur more frequently when taking immunosuppressants. These infections often affect the respiratory tract. Are usually mild. More severe infections may occur in rare cases. Therefore, please contact us in case of corresponding symptoms (e.g. B. (e.g. fever, cough, shortness of breath, sputum) should be reported to your doctor at an early stage.
And with all drugs given as infusion, infusion reactions can occur. These are flu-like symptoms such as fever, fatigue and chills, which are usually mild. However, the team in the practice where you receive the infusions is trained in such side effects and can initiate appropriate countermeasures.
MTX may cause damage to the unborn child. Women are therefore not allowed to become pregnant under MTX and up to six months after the end of MTX therapy. This also applies to men who are treated with MTX: They should not father a child during MTX therapy and also up to six months after the end of treatment. Under MTX, blood tests must also be performed regularly, and certain side effects may occur. Your doctor will inform you about this.
Another side effect of cyclophosphamide is damage to the urinary bladder. Therefore, you will receive a drug that protects the bladder mucosa at the same time as cyclophosphamide administration. This medication is called mesna. Mesna should always be administered in the morning. In addition, drink with plenty of fluids.
Common side effects of azathioprine include changes in blood counts, infections, nausea and loss of appetite.
Other than the possible infusion reactions listed above, side effects are rare with rituximab therapy. There is a slightly increased risk of infections, especially of the respiratory and urinary tracts. You should pay special attention to any signs of an infection that lasts longer than usual, and then see your doctor immediately. For more information on possible other side effects of vasculitis therapy, please ask your doctor. Information on the individual drugs can also be found on the homepage of the German Society for Rheumatology.